Tumor incidence in Visna virus inoculated mice.

Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8-12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in non-infected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma.     

Inhibition de la cancérogenèse spontanée chez les souris R III et AkR par des implants de tissus cancéreux modifiés

Summary (1) After a 24-h passage in a rabbit, fragments of spontaneous isologous mammary carcinoma were implanted under the skin of young R III females. This procedure was found to prevent the appearance of spontaneous mammary tumours in a high percentage of these animals. The subsequent appearance of carcinoma was to be observed in only 23% of treated animals as compared with 51% in controls.(2) After a 24-h passage in a rabbit, fragments of leukotic isologous tissue, implanted subcutaneously in young AkR females, reduced subsequent spontaneous leukomogenesis from 85 to 38%.     

Persistent and atypical lobules in the human breast may be precancerous.

Persistent human mammary lobules (PL) remaining after the menopause, and certain atypical lobules (ALA) are morphologically similar to the common preneoplastic hyperplastic alveolar nodule (HAN) of mice of strains having a high incidence of mammary carcinoma. This and other evidence suggest that like the HAN of mice human PL and ALA are precancerous.     

Persistent and atypical lobules in the human breast may be precancerous

Summary Persistent human mammary lobules (PL) remaining after the menopause, and certain atypical lobules (ALA) are morphologically similar to the common preneoplastic hyperplastic alveolar nodule (HAN) of mice of strains having a high incidence of mammary carcinoma. This and other evidence suggest that like the HAN of mice human PL and ALA are precancerous.This work was supported by a contract from the National Institutes of Health. PHS NOI-CB-43908, and funds from the Cancer Research Coordinating Committee, University of California.     

Molecular mechanisms of melatonin’s inhibitory actions on breast cancers

Melatonin is involved in many physiological functions and it plays an important role in many pathological processes as well. Melatonin has been shown to reduce the incidence of experimentally induced cancers and can significantly inhibit the growth of some human tumors, namely hormone-dependent cancers. The anticancer effects of melatonin have been observed in breast cancer, both in in vivo with models of chemically induced rat mammary tumors, and in vitro studies on human breast cancer cell lines. Melatonin acts at different physiological levels and its antitumoral properties are supported by a set of complex, different mechanisms of action, involving apoptosis activation, inhibition of proliferation, and cell differentiation.     

Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma.

Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.     

Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma

Summary Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vitro cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.     

Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human -lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004     

Changes in lactic dehydrogenase isoenzyme pattern in muscle of tumor-bearing mice

Summary The lactic dehydrogenase isoenzyme distribution shifts gradually toward the isoenzyme pattern of the tumor in mouse muscles located distally from a transplanted mammary carcinoma.This study was supported by a grant from the Minnesota Masonic Memorial Cancer Research Fund and, in part, by Grant No. 16-P-5681015-17 from the Rehabilitation Services Administration, U.S. Dept. of Health, Education and Welfare.     

Ultrastructural aspects of the cell fusion induced by Visna virus on sheep choroid plexus cell in culture]

Sheep choroid plexus cells infected with low multiplicities of infection of Visna Virus were stellate and had long and thin processes containing filaments and forming cytoplasmic bridges between adjacent cells. Enlargement of the bridges resulted in the formation of multinucleated cells. Some glycoproteins were clustered on filaments outside the cell. The cytoplasmic changes showed : an intensive protein synthesis; numerous mitochondria closely associated with filaments and some lysosomes and numerous vesicules near the plasma membrane.     

Alteration in the secretion of anterior pituitary hormones during dimethylbenzathracene induction of mammary tumors in rats]

In a sensitive strain of Rat (Sprague-Dawley) a deregulation of the secretion of some pituitary hormones was noted in the female during induction of mammary tumors by dimethylbenzanthracene administration. The deregulation occurred quickly and depended on the stage of the estrous cycle. It mainly consists of hyposecretion of gonadotropins. TSH and GH and of hypersecretion of prolactin.     

Ureido-ethyl-imidazolines active against autochthonous diethylnitrosamine-induced epidermoid,papillary and adenocarcinomatous tumors of the respiratory tract of Syrian hamsters and against human bronchogenic carcinomas in nu/nu mice

Summary The detection of a new class of tumor inhibiting substances is described. Employing a chemical reaction discovered several years ago, a series of imidazolinylureas were prepared. It was found that some compounds of this group were active against diethylnitrosamine (DENA)-induced tumours in hamsters. CGP 15 720 A (1-{2-[2-(4-pyridyl)-2-imidazoline-l-yl]-ethyl}-3-(4-carboxy-phenyl)urea,Xb), the most active compound at present, was developed through a series of structural variations. CGP 15 720 A inhibits significantly in oral or parenteral treatment with well tolerated doses (10–30 mg/kg) the progressive growth of autochthonous, DENA-induced papillary, epidermoid and adenocarcinomatous tumors of the respiratory system in Syrian hamsters and prolongs significantly the survival. The substance also inhibits significantly the growth of 2 poorly differentiated human epidermoid or anaplastic bronchogenic carcinomas in nu/nu Balb/c mice and prolongs the mean survival time. In these mice, the substance is also active against the rodent ascites tumors Ehrlich carcinoma, CrSa 180 and Yoshida Sa AH 66, although it is only marginally active or inactive against these tumors in normal mice or rats. — In the therapeutic trials, hamsters tolerated the highest dose administered for 4 weeks, 1000 mg/kg p.o., without signs or symptoms of toxicity.Editorial remarks. There is still an urgent medical need for effective and welltolerated drugs for the treatment of the most common forms of cancer, such as bronchial carcinoma, or for post-operative prophylaxis against relapse and metastasis. — The old-established screening method based on rapidly proliferating acute transplantable lymphatic leukemias in the mouse that is applied in the major cancer research centers has certainly achieved some measure of clinical success, inasmuch as the mean duration of survival of patients with acute lymphatic leukemia has increased from 3 months to about 6 years and similar activity has been found in some rapidly proliferating lymphomas, sarcomas and teratomas.The authors were convinced, however, that chemotherapeutic agents effective against lung cancer could only be found with the help of new specific animal models. They developed a model of an autochthonous tumor in the hamster, applied it in extensive series of experiments, and succeeded in synthesizing and identifying a group of compounds that were both effective and well tolerated. They describe the synthesis and biological activity of CGP 15 720, the compound with the highest therapeutic index and an apparently non-cytotoxic mode of action.     

CT诊断甲状腺肿块18例临床分析

目的探讨甲状腺肿块的CT诊断价值。方法回顾分析18例甲状腺肿块的CT特征,并与手术病理对照。结果CT诊断18例甲状腺肿块与手术病理符合率的情况：（1）结节性甲状腺肿7例,诊断符合率71％（5／7）;（2）甲状腺腺瘤8例,诊断符合率63％（5／8）;（3）甲状腺癌3例,诊断符合率67％（2／3）。结论CT对甲状腺肿块的诊断虽然有很大价值,但是部分甲状腺肿块CT表现无特征性,定位诊断准确,定性诊断困难。     

Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide.

Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation.     

Lipid peroxidation,low-level chemiluminescence and regulation of secretion in the mammary gland

In mammary explants of lactating mice, changes in the intensity of chemiluminescence (CL) were observed after the addition to the incubation medium of hormones and mediators that are involved in the regulation of secretion: oxytocin, acetylcholine, epinephrine and norepinephrine. A 15-min period of treatment with oxytocin, epinephrine or norepinephrine changed the level of thiobarbituric acid-reactive substances (TBARS). Two mammary explants, one of which was treated with oxytocin, acetylcholine, epinephrine or norepinephrine, were found to interact even when separated by a quartz glass wall. Analysis of the level of TBARS formation in these two explants showed that the observed interactions might be connected with light emission resulting from lipid peroxidation (LP) processes. The possible role of LP and low-level CL in the regulation of mammary gland secretion is discussed.     

Newly synthesized elastin is associated with neoplastic epithelial cells in human mammary carcinoma

Summary Indirect immunofluorescence with a purified antiserum to human foetal elastin has identified newly synthesized elastin on the membranes of neoplastic epithelial cells in human mammary carcinoma.This research was supported by a project grant from the Medical Research Council, London.     

Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide

Summary Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide\HCl. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of⁶⁰Co radiation.Research support received from United States Atomic Energy Commission Contract No. W-7405-eng-48 with the Lawrence Berkeley Laboratory.     

Establishment and characterization of 3 human cell lines derived from intracerebral metastatic tumors]

Twelve human tumors were cultivated in vitro by the trypsinization technique and 3 cell lines were established. Each of these 3 lines showed individual characteristics which were maintained during passages. After inoculation into nude mice, 2 lines induced tumors which possessed the histologic features of the original human tumors (melanoma and carcinoma of stomach), the other line derived from a breast carcinoma was rejected.     

Comparison of exogenous cell fusion induced by a wild and two mutant strains of sheep Visna virus]

Exogen cell fusion induced in vitro by a wild strain of Visna virus of Sheep is compared with two mutant strains isolated from the precedent. One of them produces large plaques in vitro (strain LPF), and the other produces small plaques (strain SPF). These strains behave in different ways according to infection multiplicity, type of cells, temperature and timing of fusing activity. Taking the wild strain K 796 as a base of reference, the strain SPF seems to have a higher rate fusing activity and the strain LPF lower rate of fusing activity.     

Glutathione andγ -glutamyl cycle enzymes in rat mammary gland

Summary The main enzymes of theγ-glutamyl cycle during the lactogenic cycle in rat mammary gland were studied. A significant increase was found in all of them with the onset of lactogenesis. The effect of methionine sulfoximine on reduced glutathione concentration was studied in tissue slices of lactating mammary gland. The findings suggest that this compound affects glutathione synthesis by inhibitingγ-glutamylcysteine synthetase. This work was supported by grant B1138-8223 from the Servicio de Desarrollo Cientifico, Universidad de Chile.